Composition for the treatment of burns, diabetic wounds, other types of wounds and subsequent lys greatly reduced scarring

ABSTRACT

Antimicrobial peptides represent a relatively new discovery in the immune system path-way. 
     Recent designs of synthetically engineered antimicrobial peptides have demonstrated increased potency and efficacy/tolerability, enhanced specificity, and reduced toxicity in comparison. 
     One such peptide, XYLENTRA, has showed significant promise from significant in vitro studies against a large number of pathogens through to extensive animal studies and is very solute resistant. These types of antimicrobial peptides show enormous promise in treating patients with chronic wounds or burn wound sepsis. The test compound Xylentra® showed significant antibacterial activity on test organisms  Staphylococcus aureus  MTCC 96 and  Pseudomonas aeroginosa  MTCC 741. 
     A substantial decrease in the microbial population level was observed in animals treated with peptide using the protocol described in detail in the application.

This application claims priority date of Provisional Application No.62/070,481 filed on Aug. 26, 2014

FIELD OF THE INVENTION

This invention relates to a novel composition of cream that can be usedwith proprietary synthetically designed bioactive peptides for thetreatment of wounds. This augmented cream can be used to specificallytreat burns and chronic wounds such as those found in diabetic woundsand eroded or cracked tissue particularly on the extremities. It isshown to significantly accelerate healing and protect patients frominfection. Treatment of wounds with the cream also greatly reducesscarring.

BACKGROUND OF THE INVENTION

Burn Wounds

Over 1.5 million people suffer burns each year in the United States.More than 5,000 of these people will die as a direct result of thesignificant loss of the skin's integrity and subsequent bacterialinvasion into the unprotected internal milieu of their bodies. Sepsisaccounts for greater than 50% of the deaths related to patients whosuffer from burns. Transmission of multi-resistant organisms to otherpatients, particularly in contained burn units, not only increasesmorbidity, but also adds an enormous cost to the healthcare system.

The current treatment of the burned patient involves fluidresuscitation, hemodynamic stabilization and the application of topicalantimicrobials prior to wound excision and grafting. Bacteria flourishin dead tissue and intravenous antibiotics cannot penetrate this tissuebecause of its impaired blood supply. This necessitates the use oftopical antimicrobials that are meant to curtail the systemic invasionof bacteria. Unfortunately, the commonly employed topical antimicrobialsare often not enough to prevent the fatal consequences of burn woundsepsis. Synthetic antimicrobial peptides are specific proteins designedto encompass a greater spectrum of activity against bacteria (includingmulti-drug resistant organisms) and fungus than traditional topicalagents.

Our proprietary peptide designs are extremely stable in hostile,non-physiologic environments. Alterations in the wound milieu,characteristics of burns, do not affect the potency or properties of thepeptide making the designed peptides more effective and valuable topractitioners who manage burns, and infected or adversely colonizedwounds. Sufficient promise was shown by several peptides through invitro and in animal studies, to lead to the selection of one to betested in several human clinical trials.

An initial double blind randomized, phase II/III clinical trial for theevaluation of a cream based peptide preparation in the topical treatmentof burn wounds was conducted at Gandhi Medical College Hospital inHyderabad, India in 2008. The mean duration to reach the total woundclosure for peptide treated patients was found to be 8.4 days while theplacebo group was 11.1 days. This was statistically significant at the(P<0.001). A second study consisting of 120 burn patients, begun in late2008 was carried out at two hospitals in Hyderabad, India. In thesestudies the patients received no additional antibiotic therapy and noneof the wounds were debrided. The final report indicated that there wereno infections and significant accelerated healing with minimal scarringand the patients had significantly fewer hospital visits.

A final phase III study was recently completed utilizing a new creamcomposition combined with a very effective designed antimicrobialpeptide. The results of this trial are found in this application.

Chronic Wounds

The loss of the skin's protective barrier as the result of unhealedwounds fosters the susceptibility to bacterial infection, invasion, andsepsis. About 40 million chronic wounds are treated globally annually.Those are wounds that get stuck in the inflammatory stage of woundhealing and do not heal. Chronic wounds are the source of severeemotional and physical stress for patients and create a significantfinancial burden, both on patients and the whole healthcare system. Inthe chronic wound the balance between production and degradation ofproteins is lost and degradation plays too large a role.

Chronic wounds present an enormous physical, social and economic burdenworldwide and their incidence is on the rise with an aging population.It has been estimated that chronic wounds affect 120 per 100,000 peopleaged between 45 and 65 years and increases to 800 per 100,000 peopleaged over 75 year. Chronic wounds result from a number of differentcauses among them diabetes, pressure, atrial and venous insufficiency,vasculitis and burns. Additional complications, including infections,necrosis, tissue hypoxia, and exudates represent further challenges indealing with a chronic wound. Poor nutrition, obesity, excessive alcoholconsumption and smoking can then add an additional layer ofcomplications to an already serious condition.

Normal wound healing progresses through three stages. The first isInflammation that lasts 2 to 4 days from the time of injury. Upon injuryhemostasis causes vascular constriction, and thrombus formation.Platelets in the wound release factors that recruit neutrophils andmonocytes (macrophages), which in turn attract lymphocytes andfibroblasts to the site of injury. The proliferation stage overlaps theinflammatory stage, starts at about day 3 and lasts for several days. Itis characterized by angiogenesis, collagen formation andepithelialization mediated by fibroblasts, and is complete when balanceis achieved in collagen formation and its continuous breakdown by matrixmetallo-proteases (MMPs). The Remodeling stage is the third and laststage and can extend over a year or more. Collagen remodeling continues,fibroblasts differentiate into myofibroblasts, vascularity decreases andtissue strength increases.

Bedsores, more properly known as pressure ulcers or decubitus ulcers,are lesions caused by many factors such as: unrelieved pressure;friction; humidity; shearing forces; temperature; age; continence andmedication; to any part of the body, especially portions over bony orcartilaginous areas such as sacrum, elbows, knees, and ankles. Althougheasily prevented and completely treatable if found early, bedsores areoften fatal—even under the auspices of medical care—and are one of theleading iatrogenic causes of death reported in developed countries,second only to adverse drug reactions.

Results from a small trial utilizing a modified version of the burncream are presented herein for the treatment of chronic wounds.

Cracked Heels

Cracked heels are a common foot problem and are often referred to asheel fissures. Cracked heels are commonly caused by dry skin (xerosis),and made more complicated if the skin around the rim of the heel isthick (callus). For most people this is a nuisance and a cosmeticproblem but when the fissures or cracks are deep, they are painful tostand on and the skin can bleed—in severe cases this can becomeinfected.

The skin is normally dry and may have a thick callus that appears as ayellow or dark brown discolored area of skin, especially along theinside border of the heel. Cracks in the skin are usually obvious.

If the cracks are severe enough, there will be pain upon weight bearingthat is not there when weight is off the heel. The edges or rim aroundthe heel will generally have a thicker area of skin (callus). Wearingopen or thin-soled shoes usually make the symptoms worse.

Some people tend to have a naturally dry skin that predisposes them tothe cracks. The thickened dry skin (callus) around the heel that is morelikely to crack is often due to mechanical factors that increasepressures in that area. Other factors that can be involved in the causeof cracked heels include:

-   -   prolonged standing (at work or home, especially on hard floors)    -   being overweight (this increases the pressure on the normal fat        pad under the heel, causing it to expand sideways—if the skin is        not supple and flexible, the pressures to ‘crack’ are high)    -   open back on the shoes (this allows the fat under the heel to        expand sideways and increases the pressure to ‘crack’)    -   some medical conditions predispose to a drying skin (e.g.        autonomic neuropathy in those with diabetes leads to less        sweating; an underactive thyroid lowers the body's metabolic        rate and there is a reduction in sweating, leading to a dryness        of the skin)    -   skin conditions (e.g. psoriasis and eczema).

Results from a small trial utilizing a modified version of the burncream are presented herein for the treatment of cracked heels.

SUMMARY OF THE INVENTION Background

Both the nature of the wound and microorganism-specific factorsinfluence the rate of microbial proliferation in and penetration of thewound tissue. The wound is rich in coagulated protein and well hydratedby the trans-eschar movement of fluid and serum, creates an excellentmicrobial culture medium. The eschar is avascular owing to thrombosis ofnutrient vessels, limiting both the delivery of systemicallyadministered antibiotics and the migration of phagocytic cells into theburned tissue. Bacterial proliferation in the wound also can be enhancedby such factors as wound maceration, pressure necrosis, and wounddesiccation with neo-eschar formation. In addition, secondary impairmentof blood flow to the wound could further predispose the patient toinvasive infection by curtailing the delivery of oxygen, nutrients, andphagocytic cells to the viable sub-eschar tissue.

The character of the microbial flora of the burn wound changes with timeand Gram-negative organisms replace Gram-positive organisms thatpredominate in the early post wound period by the second week. Withoutthe application of topical antimicrobial agents, the density of bacteriaprogressively increases, and the microorganisms penetrate the eschar bymigration along sweat glands and hair follicles until they reach theeschar/nonviable tissue interface. If the density and invasiveness ofthe microorganisms exceed the host's defense capacity, proliferatingorganisms in the sub-eschar space can invade the underlining viabletissue, leading to invasive burn wound infection and even systemicspread to remote tissues and organs. Bacterial invasion is uncommonunless the number of microorganisms exceeds 10⁵/grams of biopsy tissue.Effective topical antimicrobial chemotherapy limits intra-escharbacterial proliferation and the attendant risk of invasive infection.

Over the past 20 years, significant changes in the microbial ecology ofthe burn wound have been noted. The recovery of Pseudomonas and othergram-negative bacteria, which were once the most common organismscausing burn wound infection, has markedly declined with improvements inthe isolation of patients. Patients who have received broad-spectrumantibiotics for perioperative coverage or treatment of septiccomplications and whose wounds remain open for many days owing to theextent of the burn are at increased risk of burn wound colonization andinfection by yeasts, fungi, and multiple antibiotic-resistant bacteria.The true fungi have replaced bacteria as the most common microbescausing burn wound infection in recent years. Pseudomonas aeruginosa,Staphylococcus aureus and Aspergillus species are the commonestorganisms associated with burn wound infection.

Mafenide acetate, 1% SSD and silver nitrate are the three most commonlyemployed topical antimicrobial agents for burn wound care. Each agenthas specific limitations and advantages.

1% SSD burn cream is most effective when applied to burns soon afterinjury to minimize bacterial proliferation on the wound's surface. Ithas limited solubility in water and, therefore, limited ability topenetrate into the eschar. With continual use, resistance to thesulfonamide component of 1% SSD is common, particularly in certainstrains of Pseudomonas and many Enterobacter species. Mafenide acetatediffuses freely into the eschar owing to its high degree of watersolubility. It is the preferred agent if the patient has heavilycontaminated burn wounds or has had burn wound care delayed by severaldays. Hypersensitivity reactions occur in 7% of patients. This agentalso inhibits carbonic anhydrase, and a diuresis of bicarbonate often isobserved after its use. The resultant metabolic acidosis couldaccentuate post-burn hyperventilation, and significant acidemia coulddevelop if compensatory hyperventilation is impaired. A 0.5% silvernitrate solution has a broad spectrum of antibacterial activity impartedby the silver ion. This agent does not penetrate the eschar because thesilver ions are rapidly precipitated on contact with any protein orcationic material.

It is clear that the topical agents are crucial in the ultimateeradication of the burn and infected wound pathogens since it isextremely difficult to administer the intravenous antibiotics tonon-perfused tissue such as burned skin. The poorly vascularized,wounded skin is, therefore, the portal of entry and the ongoing nidus ofinfection for burn victims. The ideal topical agent should be highlyactive against common and multi-resistant pathogens, such as methicillinresistant Staphylococcus aureus, vancomycin resistant Enterococcusfaecium/faecalis, and extended spectrum β-lactamase producingGram-negative organisms, while having a neutral or even beneficialeffect on the wound healing process.

Antimicrobial peptides represent a relatively new discovery in theimmune system path-way. These small peptides are inducible elements ofthe immune system that serve as nonspecific effector molecules toeradicate infection caused by bacteria, yeast, and viruses, protectinghost epithelial surfaces such as the tracheal mucous membrane andgenitourinary tract. In mammals, several of these compounds are known tobe present in high concentrations in neutrophilic granules and phagocytevacuoles. These peptides differ significantly in their structure betweenspecies but, in common, appear to create amphipathic helical orbeta-pleated structures. The mechanism of action is different fromcurrently utilized antibiotics and appears to be based on their abilityto insert into membranes, from channels or “pores”, and destroy the cellby changing membrane conductance and altering intracellular function.Based upon the principles discovered in naturally occurring peptides,recent designs of synthetically engineered antimicrobial peptides havedemonstrated increased potency and efficacy/tolerability, enhancedspecificity, and reduced toxicity in comparison. These peptides termedas designed antimicrobial peptides (dAMP), are resistant to such effectsof high solute levels and demonstrate even greater antibacterialactivity. One such peptide, XYLENTRA, has showed significant promisefrom significant in vitro studies against a large number of pathogensthrough to extensive animal studies and is very solute resistant. Thesetypes of antimicrobial peptides show enormous promise in treatingpatients with chronic wounds or burn wound sepsis. The impact of thiswould improve patient survival or quality of life and reduce costs tothe patient, their family, hospital and society.

The proprietary test compound Xylentra® showed significant antibacterialactivity on test organisms Staphylococcus aureus MTCC 96 and Pseudomonasaeroginosa MTCC 741. The test compound showed 100% killing ofStaphylococcus aureus on exposure to 1 μM (4.3 μg/ml) and 5 μM (21.5μg/ml) concentrations for 1 hr at pH 7.2, and at pH 8.4 an exposure of 4hrs was required to get 100% killing. Whereas, 100% killing ofPseudomonas aeruginosa was observed on exposure to the test compound for1 hr at pH 8.4 and an exposure of 4 hrs was required for 100% killing atpH 7.2.

The microbiological studies with Xylentra® in-vivo using a rat burnwound model were conducted. The observations on the bacterial growth ineschar and sub-eschar muscles on post burn day one, two or three inpeptide treated and control treated groups were made. A substantialdecrease in the microbial population level was observed in animalstreated with peptide.

Sub Acute Toxicity studies of (Xylentra®) in rats and rabbitsdemonstrated that it was safe.

No abnormalities in physical, physiological, biochemical andhisto-pathological parameters were observed on application of thepeptide. No mortality was seen in animals from any group. There isevidence (dermal histopathology findings) to show that Xylentra® hasstimulatory action on tissue growth (increased collagen content ingranulation tissue and re-epithelialization) thus promoting improvedwound healing (unpublished observations).

The results of a Phase-I clinical trial (n=24) on healthy human patientsrevealed that Xylentra® cream administered topically twice a day wassafe. There was an absence of any symptoms or signs of toxicity at theevaluation site and considered a measure of primaryefficacy/tolerability was established in this study. Xylentra® was safeand adverse events were found to be minimal in the Phase-I Study. Mildredness and itching was seen in 2/24 volunteers. Treatment Groups (2%and 4%) were similar in efficacy/tolerability and safety parametersstudied. Pharmacokinetic data was analyzed by HPLC at different timeintervals and suggested no systemic absorption of the drug.

It was demonstrated in a phase II study (n=120) with the Xylentra®Peptide Treatment Groups (0.02% & 0.05%) that the incidence rate ofwound healing was better in terms of time to complete wound healing andachievement of a superior overall wound evaluation score over thePlacebo Group. Scar formation was also significantly lower compared tothat in Placebo Group, indicating that treatment with Xylentra® enabledmore complete healing with less morbidity. It is safe and highlyeffective in promoting burn wound healing for patients with partialthickness burns that are less than or equal to 20% without any sideeffects. None of the Xylentra® treated volunteers developed any adversereaction. Pharmacokinetic data suggested the absence of systemicabsorption.

Description of Xylentra

The proprietary cream mixture proven to be efficacious in treating burn,chronic and cracked heel wounds is composed of a sufficient amount ofthe peptide: FAKKFAKKFAKFAKKFAKFAFAF (SEQ ID NO:1) and a cream with thefollowing composition found in Table 1.

Results of Phase III Burn Trial

Study Objective

To compare safety and efficacy of 1% SSD with Xylentra in patients withpartial thickness burns in India.

In India about 60,000 people suffer from burns annually, more than50,000 are treated in hospitals and about 10,000 succumb to thermalinjury. Exact figures are likely to be even higher, considering thepoverty, illiteracy, poor standards of safety at home and industry. Thusthe burn ‘disease’ is endemic in India. House and structuale fires areresponsible for >70% of the yearly 3,785 burn-related deaths, 75% ofwhich result from smoke inhalation or asphyxiation and 25% are due toburns. Injuries due to contact with flame or ignition of clothing arethe most common cause of burn in adults whereas scald burns are mostcommon in children. The majority of patients sustain burns of suchlimited severity and extent (>80% of burns involve <20% of the bodysurface) that they can be treated on an outpatient basis. Approximately33% of patients who require in-hospital care have a major burn injury asdefined by the American Burn Association on the basis of burn size,causative agent, and associated injuries and should be treated in atertiary care burn center.

Study Population

Patients of either gender with partial thickness burns referred to atertiary referral center

Number of Subjects Enrolled: 160

Methodology

-   -   1. Study Design        -   a. Multi-center, double-blind, randomized parallel design            study in 200 patients of partial thickness burns    -   2. Study Period        -   a. 12 months    -   3. Study Procedure        -   a. Participants satisfying the inclusion criteria were            hospitalized for the study duration and were randomized in a            1:1 ratio to receive either SSD 1% or Xylentra.            Randomization was done specific for each center. Allocation            concealment was maintained. The drugs were topically            administered once daily for 4 weeks or until complete wound            healing, whichever was earlier. The patients were discharged            only after complete healing of wound and recovery from other            secondary effects of burns. A follow up was done on the            3^(rd) month to record the frequency of scars¹⁰, keloids or            contracture formation.        -   b. Key Criteria for Inclusion/Exclusion:            -   i. Inclusion:                -   1. Either sex                -   2. Age 18-60 years                -   3. Those diagnosed with partial thickness thermal                    burns as per clinically                -   4. Total surface area of the burn 10-20% as per                    Wallace rule of nine                -   5. Willing to give written informed consent.                -   6. Females of child-bearing potential with a                    negative urine pregnancy test on Day 1                -   7. Weight range within 20% of the ideal body weight                    as per standard tables and Indian criteria            -   ii. Exclusion:                -   1. History of intercurrent illnesses                -   2. History of drug addiction                -   3. History of chronic GI, renal, hepatic,                    respiratory, infectious, or History of allergy or                    hypersensitivity to investigational drugs                -   4. Chronic smokers and/or history                -   5. Patients with pulmonary burn                -   6. Patients with chemical or electrical burns                -   7. Patients taking any antibiotics

Investigational Product

Xylentra

Dose

4 gms/1% burn

Mode of Administration

Topical

Duration of Treatment

For 4 weeks or till the day of complete wound healing whichever wasearlier.

Criteria for Evaluation

Primary Variable

-   -   1. Proportion of patients having complete closure/healing of the        wounds during 28 days        -   a. Time points to measure endpoint:        -   1, 4, 6, 8, 10,12,14,16,18, 20, 22, 24, 26 and 28±1 days

Primary Variable

-   -   2. Proportion of patient with controlled secondary infection        during 28 days        -   a. Time points to measure endpoint:        -   1, 4, 8, 12, 16, 20, 24 and 28±1 days

Secondary Variables

-   -   1. Extent of non-viable tissue by clinical evaluation % of wound        covered with non-viable tissue (clinically)        -   76-100%        -   51-75%        -   26-50%        -   1-25%    -   No Necrotic Tissue    -   2. Degree of granulation by visual Score % of wound filled with        granulation tissue (clinically)        -   No Granulation        -   Scanty Granulation        -   Healthy Granulation    -   3. Wound Evaluation Done on Four Parameters (clinically):        -   Erythema (redness of the skin caused by dilatation and            congestion of the capillaries, often a sign of inflammation            or infection)        -   Edema (excessive accumulation of serous fluid in tissue            spaces)        -   Purulence (the state or condition of containing or secreting            pus)        -   Necrotic Tissue (dead, devitalized tissue)

Each of these parameters is measured on a scale of 0-3 as follows:

0=Absent; 1=Mild; 2=Moderate; 3=Severe.

4. Complete closure/healing of the wound (clinically). [Time Frame (indays): Admission to burn unit to 100% wound healing]

-   -   -   a. Time points to measure secondary endpoint: 1, 4, 6,            8,10,12,14, 16,18, 20, 22, 24, 26 and 28±1 days.

Safety

Safety was measured by pretreatment and post treatment biochemicalinvestigations (Hematological variables) and physical examination.Subjects were thoroughly monitored for adverse effects.

Conclusions

One hundred and sixty patients completed the study. The objective was tocompare the safety and efficacy of Xylentra with Silver Sulfadiazine inpatients with partial thickness burns. The patients were topicallyadministered with either Xylentra™ or Silver Sulfadiazine cream based onallocation concealment once daily for 4 weeks or until complete woundhealing whichever is earlier.

The study met its primary endpoints. The proportion of patients withcomplete wound closure was statistically significant between theXylentra and Silver Sulfadiazine group. The patients with complete woundclosure were 75 (94%) (N=80) and 65 (81%) (N=80) in the Xylentra andSilver Sulfadiazine groups, respectively in the four week time period.Moreover, Xylentra demonstrated accelerated healing rates when comparedto Silver Sulfadiazine. The time taken for complete wound closure wasfound to be less in Xylentra group compared to Silver Sulfadiazine groupas more number of patients had complete wound closure at various timepoints in the Xylentra group when comparison to the Silver Sulfadiazinegroup. Cumulative wound healing was found to be better in Xylentra groupwhen compared to Silver Sulfadiazine group. Cumulative wound healing was85.42% Xylentra™ group and 78.71% in Silver Sulfadiazine.

Burn wounds are a richer source of infection than surgical wounds,primarily because of the larger area involved and longer duration ofpatient stay in the hospital. In this study, clinical and statisticallysignificant differences were found in the proportion of patients withcontrolled secondary infections between the groups. Xylentra showedincreased efficacy in controlling the infection rate as evident from41.7% of patients with controlled secondary infection in the Xylentragroup when compared to 25% of patients with controlled secondaryinfection in Silver Sulfadiazine group. Additionally, antibiotic usagewas lower by patients in the Xylentra™ group when compared to the SilverSulfadiazine group.

Most commonly encountered and clinically significant impediments towound healing are the presence of non-viable tissue and granulation.Xylentra proved to be efficacious in controlling both non-viable tissueand granulation throughout the study period. Both the evaluation of meanscore of non-viable tissue and patient wise evaluation confirmed thatXylentra remarkably reduced non-viable tissue and granulation incomparison to Silver Sulfadiazine. On study termination day, nonon-viable tissue was found in 78 (97.50%) and 71 patients (88.75%) inXylentra and Silver Sulfadiazine groups, respectively. It was clinicallyobserved that non-viable tissue became necrotic tissue in the SilverSulfadiazine treated patients. However non-viable tissue appeared duringthe initial visits in Xylentra treated patients but no necrotic tissuewas observed during the study period. Similarly, at the end of studytermination day, the number of patients observed with no granulation inXylentra group was 75 (93.75%) and 63 (78.75%) in the SilverSulfadiazine group.

Xylentra also proved to be potent in wound evaluation based on clinicalparameters. It was effective in controlling edema, erythema andpurulence as evident from the results of mean score analysis and patientwise analysis. Patients with no edema, no erythema and no purulence werefound to be less in number in Xylentra group when compared to SilverSulfadiazine group. On study termination day, no erythema was found in78 (97.50%) and 74 patients (92.50%) in Xylentra and Silver Sulfadiazinegroups respectively. No edema was found in 79 (98.75%) and 74 (92.50%)in Xylentra and Silver Sulfadiazine groups, respectively. No purulencewas found in 78 (97.50%) and 74 (92.50%) patients in Xylentra and SilverSulfadiazine groups, respectively. In addition, the mean scores oferythema, edema and purulence were found to be considerably lower inXylentra group in comparison to Silver Sulfadiazine group.

In addition to these primary efficacy and secondary efficacy endpoints,other variables that demonstrate the potency of the drug such as drug'sability to reduce scar (pigmentation and thickness), itching andbreaking were evaluated. Scar maturation and normal skin formationalways will be depending on the quality of wound healing. Patients ofpost-burn contractures, scars defects and disfigurements constitutealmost half of the workload of many general plastic surgeons; especiallythis will directly increase the cost to patient for surgical procedures.Hence choosing the quality healing medicine is very important step inburn wound management. The clinical observations showed that most of theXylentra treated patients' wound area returned to their normal skincolor without any scar or contracture formation. However, most of thepatients treated with Silver Sulfadiazine had dark pigmentation withhypertrophic scars with contractures. Hyper pigmentation and hypopigmentation was significantly less in Xylentra group (13% and 16%) whencompared to Silver Sulfadiazine group (25% and 21%). The area with paperthin and hypertrophic scar was more than twice in Silver Sulfadiazinegroup (6% and 25%) when compared to Xylentra group (2% and 12%). Itchingwas found significantly greater in treated patients (51%) in SilverSulfadiazine group in comparison to Xylentra group (14%). In addition,18% of treated patients in Silver Sulfadiazine group had breaking ofskin in comparison to 3% of treated patients in Xylentra. These resultsdemonstrate the fact that Xylentra has the ability to heal the woundeffectively and controlling the development of scars, pigmentation,itching and breaking.

The treatment emergent adverse events (TEAEs) observed were mostly skinrelated disorders. All the adverse events were found to be mild innature. No serious adverse events and no deaths were reported in thestudy. The adverse events frequently experienced by patients in thestudy were swelling, irritation, itching, redness and pain. All theseadverse events were observed in high percentage of patients and werepresent for longer duration in Silver Sulfadiazine group when comparedto Xylentra™ group.

Burn Wounds

A summary of the statistical measurements of the test variables islisted in Table 2. Photographic comparison of both treatments can befound in FIGS. 1A and B.

Diabetic Wound Experiments

Patients were treated with the Xylentra cream once per day for theindicated times listed on FIG. 2.

Other Types of Chronic Wounds:

Cracked Feet Experiments

Patients were treated with the Xylentra cream once per day for theindicated times listed on FIG. 3.

BRIEF DESCRIPTION OF FIGURES

FIG. 1A and FIG. 1b—Photographic comparison of both burns treatments canbe found.

FIG. 2. Patients were treated with the Xylentra cream once per day forthe indicated times listed on Figure

FIG. 3. Patients were treated with the Xylentra cream once per day forthe indicated times listed on FIG.

TABLE 1 Composition of Cream 1 Cetomacrogol-1000 2-5% 2 Stearyl Alcohol 8-15% 3 Liquid Paraffin 3-6% 4 White Petrolium Jelly 15-20% 5 PropyleneGlycol  6-10% 6 Peptide 0.05-2.0%  7 Sodium Methyl Paraben 0.1-0.2% 8Sodium Propyl Paraben 0.05-0.1%  9 Sodium Phosphate 0.1-0.3% 10 SodiumAcid Phosphate 0.01-0.03% 11 EDTA Disodium 0.01-0.03% 12 Citric Acid0.3-0.8% 13 Purified Water 50-65%

TABLE 2 Summary of Statistical Measurements of Test Variables p-valueSignificant Primary Variables Variable 1 % Patients achieving completewound 0.005 YES closure/healing Variable 2 % Patients with controlledsecondary infections 0.017 YES Secondary Variables Variable 1 % of woundcovered with non-viable tissue <0.001 YES Variable 2 Degree ofgranulation 0.026 YES Variable 3 Erythema 0.310 NO Edema 0.204 NOPurulence 0.019 YES Necrotic Tissue 0.035 YES Variable 4 Time to achievecomplete closure/wound healing <0.0001 YES Additional Variables Scarring% Normal Skin <0.001 YES % Hypertrophic Scar 0.005 YES % Paper Thin Scar0.027 YES % Raw Area 0.136 NO % Itching 0.001 YES % Breakdown of Skin0.006 YES % Normal Pigmentation <0.001 YES % Hyper Pigmented Scar 0.004YES % Hypo Pigmented Scar 0.066 NO % Mottled Scar 0.470 NO

1. The wound cream composition.
 2. The wound composition withanti-microbial peptides.
 3. The wound cream composition with thespecific anti-microbial peptide of SEQ ID
 1. 4. The wound cream for thetreatment of burns.
 5. The wound cream for the treatment of diabeticwounds.
 6. The wound cream for the treatment of other chronic wounds. 7.The wound cream for the treatment of cracked feet.
 8. The wound creamtreatment yielding significant reduction in scarring caused from wounds.25